Altered Drug Disposition and Biomarkers for Diagnosis of Chronic Inflammatory Liver Disease.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Pharmacokinetic profile of morphine and its hepatically derived metabolites.
研究概览
简要总结
One-third of the U.S. population suffers from non-alcoholic fatty liver disease (NAFLD). NAFLD is caused by diabetes and obesity, and is becoming more common. Although many people have this disease, the change in how the liver handles drugs and compounds in the body has not been studied. The purpose of this study is to investigate how advanced NAFLD changes the ability of the liver to handle both endogenous and exogenous compounds.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Man or woman between 18 and 65 years of age
- •Negative pregnancy test for women of childbearing potential
- •Negative urine drug screen
- •Healthy Subjects:
- •Normal liver function tests
- •Normal kidney function and lipid panel
- •Nonalcoholic Steatohepatitis Patients:
- •Recent liver biopsy with nonalcoholic fatty liver disease activity score at least 4
排除标准
- •History of significant alcohol use (>20 g/day) and/or illicit drug use
- •Inability to abstain from alcohol for 48 prior to study
- •Use of drugs associated with a clinical or histological picture consistent with fatty liver disease or NASH for more than 12 consecutive weeks in the year prior to screening; these include amiodarone, tamoxifen, methotrexate, glucocorticoids, anabolic steroids, tetracyclines, estrogens (at doses greater than those used for hormone replacement) or valproate/valproic acid
- •Type 2 diabetes treated with oral agents other than metformin; these include secretagogues, thiazolidinediones, alpha-glucosidase inhibitors, exenatide and pramlintide.
- •Current or recent use of bile acid sequestrants, bile acid derivatives (i.e. ursodiol) or fibric acid derivatives.
- •Current use of antioxidants such as silymarin, vitamin C, glutathione, or non-prescribed complementary alternative medications (including dietary supplements, megadose vitamins, herbal preparations, and special teas) within 30 days prior to screening.
- •Previous liver biopsy that demonstrated presence of cirrhosis.
- •Radiologic imaging consistent with cirrhosis or portal hypertension.
- •Serum creatinine of 2.0 mg/dL or greater, or on dialysis, at screening.
- •History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, severe psoriasis, rheumatoid arthritis) that could affect the assessment of biomarkers (bile acids or inflammation).
- •History of bariatric surgery.
- •BMI > 45 kg/m^2 at screening.
- •Any known hypersensitivity to opiates, opiate antagonists, or ondansetron.
- •Healthy Subjects:
- •Taking concomitant medications, both prescription and non-prescription (including herbal products and over-the-counter medications), other than oral contraceptives and multivitamins (women stabilized on hormonal methods of birth control will be allowed to participate)
- •History or other evidence of liver disease in the opinion of the study investigators.
- •BMI > 30 kg/m^2 at screening.
研究组 & 干预措施
Healthy volunteers
Subjects will be asked to fast overnight. Upon presentation, FibroScan procedure with CAP will be conducted and baseline and postprandial bile acid profile will be assessed. Then, intravenous morphine will be administered and the pharmacokinetic profile will be assessed over 8 hours.
干预措施: High fat meal (Other)
Healthy volunteers
Subjects will be asked to fast overnight. Upon presentation, FibroScan procedure with CAP will be conducted and baseline and postprandial bile acid profile will be assessed. Then, intravenous morphine will be administered and the pharmacokinetic profile will be assessed over 8 hours.
干预措施: Morphine (Drug)
Advanced nonalcoholic fatty liver disease patients
Subjects will be asked to fast overnight. Upon presentation, FibroScan procedure with CAP will be conducted and baseline and postprandial bile acid profile will be assessed. Then, intravenous morphine will be administered and the pharmacokinetic profile will be assessed over 8 hours.
干预措施: High fat meal (Other)
Advanced nonalcoholic fatty liver disease patients
Subjects will be asked to fast overnight. Upon presentation, FibroScan procedure with CAP will be conducted and baseline and postprandial bile acid profile will be assessed. Then, intravenous morphine will be administered and the pharmacokinetic profile will be assessed over 8 hours.
干预措施: Morphine (Drug)
结局指标
主要结局
Pharmacokinetic profile of morphine and its hepatically derived metabolites.
时间窗: 8 hours post dose
Morphine will be administered as a 5-min IV infusion. Pharmacokinetic profiles of morphine and morphine metabolites will be quantified in the serum over the 8-hour sampling period. Non-compartmental analysis will be performed using Pharsight Phoenix software, comparing the following parameters between healthy subjects and patients with advanced NAFLD. The maximal concentration, time of maximal concentration, elimination half-life, area under the curve, and systemic and renal clearances will be calculated for both morphine and the glucuronide metabolites. Volume of distribution and metabolic clearance will be calculated for morphine.
次要结局
- Bile acid profile(Pre- and postprandially)
- FibroScan with Controlled Attenuation Parameter (CAP) Software(No preparation (fasting) required-consumption of large meals prior to the Fibroscan procedure is not advised)
研究者
Sidney Barritt, MD
Assistant Professor of Medicine
University of North Carolina, Chapel Hill